Before talking about anything else in this blog, I would like to explain one of the pathogens that causes many diseases. The purpose is to help you better understand my future posts because some of them might be related to pathogens.
So today, I would like to talk about bacteria and one of its fundamental mechanisms. Bacteria is a single-celled microscopic organism with few genes. They live in and on other organisms such as human and grow by consuming nutrients from environment. These bacteria have symbiotic relationship with the host; mutualism, commensalism, or parasitism. The size of a bacteria is so small that individual bacteria cannot affect the host by itself but when many bacteria act together to achieve the same goal simultaneously, the effect cannot be overlooked.
Bacteria work and communicate simultaneously by recognizing other neighboring bacteria community using chemical signal molecules, autoinducers. They produce, release, detect, and recognize autoinducers for chemical communication. Quorum sensing is a mechanism which allows bacteria to monitor the environment for other bacteria and to alter behavior on a population-wide scale in response to changes in the number present in a community by detecting autoinducers.
Autoinducer concentration increases as bacterial cell population density increases. These chemical molecules accumulate and after reaching a threshold level, bacteria detect autoinducers and alter gene expression. To simply explain the mechanism, a bacterial cell has signal producing protein and it produces autoinducers intracellulary then released outside of the cell. Also, bacterial cell has signal receptor protein for autoinducer. When autoinducers’ concentration passes a threshold, autoinducer binds to receptor protein triggering signal transduction cascade that result in population-wide changes in cells’ behavior. However, when a single bacteria performs the mechanism it is futile since there are no other bacteria to receive the signal and concentration of autoinducers cannot reach the threshold.
Pathogenic bacteria use quorum sensing to promote virulence factor expression to cause disease. For example, “S. aureus” is a very dangerous opportunistic pathogen which has been incresingly associated with antibiotic resistance. One of the factors that contribute to “S. aureus” virulence is its peptide-based quorum sensing system and regulation of biofilm formation, a central factor in S. aureus virulence.The accessory gene regulator (agr) system is intricately involved in the regulation of virulence genes P2 and P3 which produce RNA II and RNA III. Transcription from P3 leads to production of the effector molecule of the agr system, RNA III. RNA III functions to increase the production of capsule, toxins, and proteases. One of virulence factors regulated by agr contains genes involved in production of exoproteins associated with invasion and toxin production. Thus, activation of agr system in “S. aureus” turns the bacterium from commensal to aggressive and invasive pathogen.
As quorum sensing controls virulence, it has been considered an attractive target for the development of new antobiotics. One way is making disease-specific anti quorum sensing molecule for intra-specific communication. It looks similar with autoinducer and binds to receptor but does not initiate signal transduction cascade, thus, inhibiting virulence. The other way focuses on inter-species communication. It works similarly with the disease-specific anti quorum sensing molecule but the molecule binds to inter-species receptor so the cell cannot recognize other surrounding bacteria. It is targetted to be used as broad spectrum antibiotics that work against all bacteria.